Phase II Trial of Thalidomide in the Treatment of Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck

Patients with recurrent squamous cell carcinoma of the head and neck
have a poor prognosis. Thalidomide (Thalomid) has antitumor and
antiangiogenic properties. We conducted a phase II trial to determine
toxicity, response rate, and survival in patients with recurrent
squamous cell carcinoma of the head and neck. Eligibility criteria
included recurrent and/or metastatic squamous cell carcinoma of the
head and neck, measurable disease, and two or fewer prior
chemotherapy regimens.

Thalidomide was administered at a starting dose of 200 mg nightly and
increased by 200 mg every week to a goal dose of 1,000 mg nightly.
Women of childbearing potential and pregnant women were excluded. Of
17 patients enrolled in the study to date, there are 12 males (71%)
and 5 females (29%); the median age is 56 years. Patients received
extensive prior treatments: 94% chemotherapy, 88% radiation therapy,
and 77% surgery.

The most frequent toxicities included fatigue in 94% of patients
(grade 3/4 in 19%), nausea/vomiting in 41% (grade 3/4 in 14%), edema
in 53% (grade 3/4 in 22%), constipation in 35% (grade 3/4 in 0%),
sensory neuropathy in 47% (grade 3/4 in 0%), pain in 35% (grade 3/4
in 0%), and skin reaction in 24% (grade 3/4 in 0%).

The median duration of treatment on protocol was 1.25 months. Of 17
patients treated, 16 (94%) have shown progressive disease and 1 (6%)
was inevaluable due to early death. The median survival time for the
17 patients is 5.4 months. A subset of patients underwent baseline
and posttreatment tumor biopsies to assess correlative biology.
Currently, analysis of biopsies for angiogenic assays is underway and
will be presented at the meeting.

CONCLUSION: We found that thalidomide is well tolerated in
this population of heavily pretreated patients with recurrent
squamous cell carcinoma of the head and neck, with a minority
experiencing grade 3/4 toxicity. Thus far, the response rate for
thalidomide in this population of patients is low, with median
survival similar to that of historical controls.